P928: OCULAR ADVERSE EVENTS AND FUNCTIONAL IMPACT IN TRANSPLANT INELIGIBLE, NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS TREATED WITH BELANTAMAB MAFODOTIN, LENALIDOMIDE AND DEXAMETHASONE IN A PHASE 1/2 TRIAL
Authors: Evangelos Terpos, Ioannis Ntanasis-Stathopoulos, Maria Gavriatopoulou, Panagiotis Malandrakis, Despina Fotiou, Magdalini Migkou, Foteini Theodorakakou, Vasiliki Spiliopoulou, Rodanthi Syrigou, Evangelos Eleutherakis-Papaiakovou, Stavros Gkolfinopoulos, Kyriaki Manousou, Efstathios Kastritis, Meletios A. Dimopoulos
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Ocular adverse events (OAEs), manifesting as visual acuity changes, ocular symptoms, and corneal findings, are common with belantamab mafodotin (belamaf; GSK2857916) and the main reason for dose modifications. Here, we present the OAEs and the associated functional impairment in patients (pts) from the phase 1/2 BelaRd study. Aims: To present the OAEs and their impact on daily activities in transplant-ineligible (TI), newly diagnosed multiple myeloma (NDMM) pts treated with belamaf plus lenalidomide and dexamethasone (Rd). Methods: BelaRd (NCT04808037) is an ongoing, prospective, open-label phase 1/2 study that aims to enroll 66 TI, NDMM pts. In Part 1, which investigates the safety/clinical activity of belamaf plus Rd, 36 pts are randomized (1:1:1) to receive belamaf at doses of 1.4, 1.9 or 2.5 mg/kg Q8W. Ocular exams include assessment of best corrected visual acuity (BCVA) via the Snellen chart and slit lamp corneal evaluation. Ocular symptoms are graded according to CTCAE v5.0 and dry eye disease severity and activities of daily living (ADLs) are assessed using the Ocular Surface Disease Index (OSDI). This descriptive analysis included all Part 1 pts (cut-off date: 15/12/2022). Results: At baseline, all pts had ocular comorbidities. Regarding ocular manifestations suggesting an impairment in vision, from a total of 499 ocular assessments, Gr2 and Gr3 BCVA changes were noted in 164 (33%) and 54 (11%), respectively, while a meaningful BCVA decline (worse than 20/50 in the better seeing eye) was observed in 38 (8%), with a median time to resolution of 1 month. Table 1 shows the analytical information on the results of the assessments per cohort. In terms of ≥Gr2 symptoms directly related to decreased vision, blurred vision and visual impairment were observed in 38 (8%) and 98 (20%) with a median time to resolution of 2 months. In terms of other ≥Gr2 ocular symptoms, observed in ≥10% of assessments, dry eye was noted in 96 (20%), with a median time to resolution of 3 months. Regarding corneal findings, in 501 slit lamp examinations, Gr2 and Gr4 keratopathy was observed in 55 (11%) and in 2 (<1%), respectively, with a median time to resolution of 4 months. The proportion of skipped/planned belamaf doses due to OAEs were 26% (24/94), 26% (28/106) and 35% (34/98) in the 1.4, 1.9 and 2.5 mg/Kg dose cohorts. In relation to OSDI findings, in the ocular symptoms category (Q1–5), the proportions of assessments with ‘all’ or ‘most’ of the time worst answers were 0%, 1% (1/173), 0% and 6% (8/146), 2% (4/173), 3% (5/146), in the 1.4, 1.9 and 2.5 mg/Kg cohorts, respectively. The proportions of assessments with ‘all’ or ‘most’ of the time worst answers in the ADL category (Q6–9) were 1% (1/146), 0%, 1% (1/146) and 1% (2/146), 2% (3/173), 3% (5/146) in the 1.4, 1.9, 2.5 mg/Kg cohorts, respectively. Summary/Conclusion: In the upfront treatment of TI, NDMM pts with belamaf plus Rd, the frequency of clinically relevant impairment in vision was low, as a meaningful BCVA decline was observed in less than 10% of assessments, with a rapid time to resolution. The impact of the combination on daily functioning was also minimal, as ‘all’ or ‘most’ of the time responses in OSDI ADL category were <3%. Table 1. Ocular characteristics of patients at baseline and after treatmentKeywords: Multiple myeloma